This proposal is for a Dental Scientist Award to support didactic and research training for Dr. Ellen Byrne, a clinical faculty member, in the basic science disciplines of Pharmacology and Toxicology as applied to research areas in the Toxicology of fluoride (F-). Overall supervision and training will be overseen by Dr. R. A. Carchman (primary sponsor) who is an established Pharmacologist/Toxicologist and a secondary sponsor (Dr. F. Knap) in the clincal areas of Prosthodontics. Phase I of this proposal is envisioned to encompass approximately two years and includes didactic course work in pharmacology, toxicology, immunology and pre-clinical course work in basic concepts of prosthodontics, periodontics, orthodontics, occlusion and dental materials. The candidate will attend and present at seminars within the University and at National Dental and Basic Science meetings. Research training in sterile tissue culture techniques, i.e. growth and maintenance and cell characterization will be included in this first phase. Other experimental techniques to be learned include methods in gel electrophoresis, measurment of superoxide anion (02-) production, N-formyl-L-methionyl-L-leucyl-L-phenylalanine and phorbol diester binding (density and affinity) and protein kinase/phosphatase activity. Phase II of this proposal is anticipated to be three years in duration. During this time skills learned in Phase I will be applied to studies in the functional and biochemical evaluation of the mechanisms involved in F- induced changes in granulocytes (e.g. 02- production) in order to define 1) the cellular site(s) in granulocytes through which F- is operating 2) the biochemical mechanisms(s) which may be operating in these pathways. Publication of abstracts and submission of manuscripts to peer reviewed journals and preparation of an individual N.I.H. research proposal will be included in this final phase. Clinical requirements for certification in prosthodontics will also be completed during Phase II.